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Biomedical subjects

I Hamilton

Publications and source records attributed to I Hamilton.

At least 19 recordsLinked to original sources

CD40 and CD86 upregulation with divergent CMRF44 expression on blood dendritic cells in inflammatory bowel diseases.

OBJECTIVE: Dendritic cells (DC) are the only antigen-presenting cells that can activate naïve T lymphocytes and initiate a primary immune response. They are also thought to have a role in immune tolerance. DC traffic from the blood to peripheral tissue where they become activated. They then present antigen and the costimulating signals necessary to initiate an immune response. In this study, we investigated the number, subsets, and activation pattern of circulating and intestinal DC from patients with clinically mild ulcerative colitis (UC) or Crohn's disease. METHODS: Patients were recruited, if they were not taking immunosuppressive therapy, and were assessed for clinical severity of their disease using for UC, the Clinical Activity Index, and for Crohn's disease, the Crohn's Disease Activity Index. Blood CD11c+ and CD11c- DC subsets, expression of costimulatory antigens, CD86 and CD40, and the early differentiation/activation antigen, CMRF44, were enumerated by multicolor flow cytometry of lineage negative (lin- = CD3-, CD19-, CD14-, CD16-) HLA-DR+ DC. These data were compared with age-matched healthy and the disease control groups of chronic noninflammatory GI diseases (cGI), acute noninflammatory GI diseases (aGI), and chronic non-GI inflammation (non-GI). In addition, cryostat sections of colonoscopic biopsies from healthy control patients and inflamed versus noninflamed gut mucosa of inflammatory bowel disease (IBD) patients were examined for CD86+ and CD40+ lin- cells. RESULTS: Twenty-one Crohn's disease and 25 UC patients, with mean Crohn's Disease Activity Index of 98 and Clinical Activity Index of 3.1, and 56 healthy controls, five cGI, five aGI, and six non-GI were studied. CD11c+ and CD11c- DC subsets did not differ significantly between Crohn's, UC, and healthy control groups. Expression of CD86 and CD40 on freshly isolated blood DC from Crohn's patients appeared higher (16.6%, 31%) and was significantly higher in UC (26.6%, 46.3%) versus healthy controls (5.5%, 25%) (p = 0.004, p = 0.012) and non-GI controls (10.2%, 22.8%) (p = 0.012, p = 0.008), but not versus cGI or aGI controls. CD86+ and CD40+ DC were also present in inflamed colonic and ileal mucosa from UC and Crohn's patients but not in noninflamed IBD mucosa or normal mucosa. Expression of the CMRF44 antigen was low on freshly isolated DC, but it was upregulated after 24-h culture on DC from all groups, although significantly less so on DC from UC versus Crohn's or healthy controls (p = 0.024). The CMRF44+ antigen was mainly associated with CD11c+ DC, and in UC was inversely related to the Clinical Activity Index (r = -0.69, p = 0.0002). CONCLUSIONS: There is upregulation of costimulatory molecules on blood DC even in very mild IBD but surprisingly, there is divergent expression of the differentiation/activation CMRF44 antigen. Upregulation of costimulatory molecules and divergent expression of CMRF44 in blood DC was also apparent in cGI and aGI but not in non-GI or healthy controls, whereas intestinal CD86+ and CD40+ DC were found only in inflamed mucosa from IBD patients. Persistent or distorted activation of blood DC or divergent regulation of costimulatory and activation antigens may have important implications for gut mucosal immunity and inflammation.

Adolescent↗

Finding ethical principles and practical guidelines for the controlled flow of patient data.

The application of computing to health care, and particularly to electronic patient records, offers major benefits but raises issues of confidentiality and of potential misuse. Sound access control mechanisms are therefore important, but most models focus upon informed consent by the data subject. This raises challenges in mental health care, and for other vulnerable patients including those comatose, and the severely ill and temporarily distressed. Published algorithms which are used to control record access within a controlled environment therefore have value, as a means of ensuring an open and informed, yet ethically sound, solution. The paper describes the background and issues, and gives an example of such an algorithm.

Computer Security↗

Towards an ethical protocol in mental health informatics.

Application of informatics to mental health has the potential to benefit a disadvantaged yet important patient group. At the same time, difficult issues are raised with regard to data protection and ethics because many patients are not able to express informed and rational views, and this increases their vulnerability. However, developments in this field are limited, and there is little literature. Generic data protection legislation and guidance assumes that data subjects are mentally competent adults. This paper distils key ethical issues and principles in mental health informatics, and describes a process which has initiated the identification of "reasonable" practice.

Adult↗

Does resuscitation produce a reperfusion injury?

Conceptually, shock with resuscitation should produce cellular changes that parallel those observed in a single organ exposed to ischemia with reperfusion, i.e., a transient worsening of the injury pattern after reperfusion with the degree of recovery reflecting the magnitude of the ischemic injury. To test this hypothesis, 74 male Sprague Dawley rats (300-400 g) were randomized into two groups with controls and exposed to 1) hemorrhagic shock (mean arterial pressure < 50 mm Hg) for 2 hours before sacrifice, or 2) shock (2 hours) with reinfusion of shed blood over 1 hour before sacrifice. Mean arterial pressure, blood loss, serum lactate, base excess, and bicarbonate were serially measured to determine the degree of tissue ischemia. At sacrifice, hepatic mitochondrial function was determined by the respiratory control ratio. Our findings were as follows: 1) Hemorrhagic shock produced significant (P < 0.001) tissue ischemia and impairment of mitochondrial function (P < 0.001), 2) resuscitation rapidly corrects the metabolic sequelae of tissue ischemia, and 3) mitochondrial function was unaffected by resuscitation. We conclude that resuscitation rapidly corrects the tissue ischemia associated with hemorrhagic shock, without producing any measurable reperfusion injury at the mitochondrial level.

Animals↗

Interethnic marriage: identifying the second generation in Australia.

"Studies in Australia show that an increasing proportion of the population have ancestors from more than one country. Evidence regarding differences in the marriage patterns of first and second generation migrants has been restricted in scope as published marriage registration data includes only birthplace of partners. Marriage registration records include information about the birthplace of parents of partners, but is available only through specially produced tabulations. Changes in the census for 1986 and 1991 make it possible to identify the second generation in households, and this article examines the use of census data as an alternative to marriage registration records in tracing changes in intermarriage patterns and differences between urban and rural areas."

Australia↗

Hepatic and cerebrospinal fluid accumulation of aluminium and bismuth in volunteers taking short course anti-ulcer therapy.

To investigate the possible absorption and deposition of bismuth or aluminium from agents used in the treatment of peptic ulcers, we have measured levels of bismuth and aluminium in the liver tissue of 15 patients undergoing elective liver biopsy and in the cerebrospinal fluid (CSF) of 15 patients undergoing elective myelography after administration of standard therapeutic doses of tripotassium dicitrato bismuthate (TBS), sucralfate or aluminium hydroxide for 1 month. Aliquots of liver or CSF were separated and levels of both aluminium and bismuth were assayed in each sample by atomic absorption spectrophotometry. The group who received TBS had significantly higher liver bismuth levels than the other two treatment groups, but there was no significant difference in CSF bismuth levels among the three groups. There was no significant difference in either liver or CSF aluminium levels among the three treatment groups. We conclude that tissue accumulation of bismuth may occur after short-course therapy with colloidal bismuth, although there is no evidence of CNS accumulation of bismuth in the present study.

Aluminum↗

Severe superior vena caval syndrome after the Mustard repair in a patient with persistent left superior vena cava.

This report describes our experience with a 6-year-old girl with dextro-transposition of the great arteries and persistent left superior vena cava, who manifested severe superior vena caval syndrome following a Mustard repair. A direct end-to-end anastomosis of the left superior vena cava to the left atrial appendage, which formed part of the systemic venous atrium, was performed with excellent relief of the obstruction. The rationale for application of this method is discussed as an alternative to the use of cardiopulmonary bypass for intra-atrial baffle revision.

Child↗

Management of a persistent pancreatic fistula secondary to a ruptured pseudocyst with endoscopic insertion of an expandable metal stent.

A case of pancreatic fistula successfully managed by the endoscopic insertion of an expanding-mesh metal stent into the pancreatic duct is reported. The patient had developed a fistula following rupture of a pancreatic pseudocyst, and attempted transpapillary drainage using plastic endoprostheses had failed due to prosthesis migration. Insertion of a Strecker metal stent was followed by rapid and sustained clinical improvement and cessation of fistula drainage.

Aged↗

Palliation of biliary obstruction in patients with advanced breast cancer using endoscopic stents.

Endoscopic insertion of a biliary endoprosthesis was successful in eight patients with extrahepatic biliary obstruction caused by breast cancer metastases. The serum bilirubin level was significantly reduced in seven patients and in four this was accompanied by marked symptomatic improvement. Endoprostheses required replacement after a median of 8 (range 3-127) weeks. Two patients responding to systemic anticancer therapy survived 27 and 43 months. Endoscopically placed stents offer effective palliation of extrahepatic biliary obstruction caused by metastatic breast cancer and long-term survival may be possible.

Adult↗

A role for endothelin and nitric oxide in the pressor response to diaspirin cross-linked hemoglobin.

Diaspirin-cross-linked hemoglobin (DCLHb; Baxter Healthcare Corp) has potential for clinical use as a hemoglobin-based oxygen-carrying solution. We have previously shown that DCLHb administration is associated with a self-limiting increase in mean arterial pressure (MAP). Based on in vitro studies with other hemoglobin solutions, this vasopressor effect is thought to be mediated at least in part by the release or inhibition (or both) of endothelium-derived vasoactive substances. The purpose of our studies was to determine the role of endothelin (ET), a potent vasoconstrictor peptide, and nitric oxide, a vasodilator, in mediating the pressor effect of DCLHb in conscious rats. Intravenous administration of DCLHb has been shown to elicit an immediate increase in MAP that peaks within 30 minutes and returns to baseline by 300 minutes in a dose-dependent fashion. Phosphoramidon, an inhibitor of proendothelin conversion to ET, attenuated the elevation of MAP when administered before DCLHb. Administration of cyanomet DCLHb, a DCLHb molecule that is unable to interact with NO, was not associated with an elevation of MAP. L-arginine, the substrate for NO synthesis, and nitroglycerin, an NO donor, significantly reduced MAP when infused 15 minutes after DCLHb administration. Based on these findings, we conclude that the DCLHb-induced elevation of MAP in vivo is mediated at least in part by ET and the inhibition of NO. Although these data support earlier reports of hemoglobin binding NO, this is the first report of the pressor response to hemoglobin being attenuated by an agent that blocks the conversion of proendothelin to ET.

Animals↗

Endoscopic management of bile duct stones at Auckland Hospital in 1988 and 1989.

OBJECTS: to define the role of endoscopic management of bile duct calculi in a tertiary referral institution. METHODS: an unselected series of 466 patients presenting for ERCP over a two year period were reviewed and 103 patients with bile duct calculi identified. The results of endoscopic management of these patients is reviewed. RESULTS: endoscopic sphincterotomy was successful in 98% of patients, and resulted in clearance of calculi from the bile duct in 75%, and in a further 8% symptoms were successfully controlled by sphincterotomy with or without endoprostheses, despite residual calculi. Seventy-nine percent of the patients with choledocholithiasis were successfully managed endoscopically, minor complications occurring in 16% which were significant in only 4%, with no procedure related mortality. CONCLUSIONS: endoscopic sphincterotomy provides a safe and effective means of managing bile duct calculi, even if stone extraction cannot be completed.

Adult↗